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Chronic cocaine exposure induces noradrenergic modulation of inhibitory synaptic transmission to cholinergic neurons of the laterodorsal tegmental nucleus
Author(s) -
Taoka Naofumi,
Kamiizawa Ryota,
Wada Shintaro,
Minami Masabumi,
Kaneda Katsuyuki
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13405
Subject(s) - neuroscience , ventral tegmental area , neurotransmission , cholinergic , inhibitory postsynaptic potential , chemistry , cholinergic neuron , gabaergic , excitatory postsynaptic potential , dopaminergic , dopamine , biology , receptor , biochemistry
The laterodorsal tegmental nucleus ( LDT ), which sends cholinergic efferent connections to dopaminergic ( DA ) neurons in the ventral tegmental area ( VTA ), plays a critical role in the development of addictive behavior and the reinstatement of cocaine‐seeking behavior. Although repeated cocaine exposure elicits plastic changes in excitatory synaptic transmission and intrinsic membrane excitability in LDT cholinergic neurons, it remains unclear whether inhibitory synaptic transmission is modulated by cocaine exposure. The LDT receives fibers containing noradrenaline ( NA ), a neurotransmitter whose extracellular levels increase with cocaine exposure. Therefore, it is hypothesized that repeated cocaine exposure induces plastic changes in LDT cholinergic neurons via NA . Ex vivo electrophysiological recordings in LDT cholinergic neurons were obtained from rats repeatedly exposed to cocaine. Bath‐application of NA induced similar levels of hyperpolarization in both saline‐ and cocaine‐treated neurons. However, NA attenuated the amplitude of inhibitory postsynaptic currents ( IPSC s) in cocaine‐ but not saline‐treated neurons through α2 adrenoceptors. This NA ‐induced IPSC attenuation was observed in the presence of strychnine, but not gabazine, indicating that NA modulated GABA ergic but not glycinergic neurotransmission. NA increased the paired‐pulse ratios of evoked IPSC s and decreased the frequencies of miniature IPSC s ( mIPSC s) without affecting their amplitudes, suggesting a presynaptic mechanism. These findings suggest that repeated cocaine exposure induces neuroplasticity in GABA ergic synaptic transmission onto LDT cholinergic neurons by probably modulating presynaptic α2 adrenoceptors. This potentially increases the activity of LDT cholinergic neurons, which might contribute to the development of addictive behavior by enhancing VTA DA neuronal activity.